STING (stimulator of interferon genes) is a pattern recognition receptor and adapter protein that is anchored in the endoplasmic reticulum (ER), and is highly expressed in immune cells. STING-dependent signaling mediates a toll-like receptor independent innate immune response following detection of cytoplasmic pathogens.
The invasion of a cell by a pathogen, such as a virus or bacterium, results in a host defence response mediated by the adapter protein STING. Foreign DNA is detected by cytosolic DNA sensors, which converge at STING to induce a signal transduction pathway, culminating in the production of proinflammatory cytokines and type 1 interferons (IFNs). STING is also activated by the bacteria secondary messenger cyclic dinucleotides (CDNs) c-di-GMP and c-di-AMP. Following detection of cytosolic DNA or CDNs, STING forms a dimer and translocates from the ER to perinuclear microsomes, where it is poly-ubiquitinated on K27 by the autophagy motility factor receptor (AMFR)-insulin-induced gene 1 (INSIG1) complex. Poly-ubiquitinated STING binds TBK1, and the STING-TBK1 complex activates the transcription factor interferon regulatory factor 3 (IRF3), which translocates into the nucleus to induce IFN gene expression.
STING is modulated by certain proteins, to ensure that the STING-dependent immune response is strong enough to eliminate invading pathogens, without being damaging to the host. The ubiquitin E3 ligases RNF5 and RNF26 promote STING proteasomal and autophagic degradation respectively, while the pattern recognition receptor NLRC3 prevents STING translocation from the ER to microsomes.
As well as having a role in innate immunity, STING has also been shown to be involved in autoimmune diseases and cancer immunology. STING has been shown to be activated by aberrant host DNA leaked from the nucleus, to induce a pro-inflammatory response. This mechanism may be of pathological importance for autoimmune diseases such as lupus erythematosus. STING-dependent signaling can also promote a T cell response against tumors, by detecting tumor-derived DNA. STING agonists administered into the tumors of mice, have been shown to induce an adaptive immune response resulting in tumor regression, thus providing a potential target for cancer immunotherapy.View all products for STING-Dependent Signaling »
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